Bax is upregulated by p53 signal pathway in the SPE B-induced apoptosis

ABSTRACT Our previous work suggested that streptococcal pyrogenic exotoxin (SPE) B-induced apoptosis is mediated through a receptor-like mechanism. In this study, we have identified αvβ3 and Fas as the SPE B receptors for this function. The SPE B fragment without the RGD motif and G308S, a SPE B mutant with the RSD motif, induced less apoptosis than did native SPE B, suggesting that the RGD motif is critical for SPE B-induced apoptosis. Fluorescein isothiocyanate-SPE B binding assays and immunoprecipitation analysis showed that SPE B specifically interacted with αvβ3. Anti-αvβ3 antibody partially inhibited SPE B-induced apoptosis but had no effect on G308S-induced apoptosis. In addition, Fas binding to SPE B was verified in an affinity column and an immunoprecipitation analysis. Anti-Fas antibody inhibited SPE B- and G308S-induced apoptosis in a dose-dependent manner, suggesting that Fas-mediated SPE B-induced apoptosis also occurs RGD independently. Both anti-αvβ3 and anti-Fas antibodies synergistically inhibited SPE B-induced apoptosis. The apoptotic cascades were activated by SPE B and G308S, with a little delay by the latter. After SPE B binding, the cell surface level of αvβ3, but not of Fas, was decreased. The decreased αvβ3 level was restored by treatment with the proteasome inhibitor MG132, suggesting a SPE B-mediated endocytosis of integrin αvβ3 via the ubiquitin-proteasome system. Taken together, our results demonstrate that SPE B-induced apoptosis is mediated through αvβ3 integrin and Fas in a synergistic manner.

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GW26-e4015 Role of Akt/mTOR signal pathway in iodine contrast agent-induced apoptosis in diabetic rat kidneys

Journal of the American College of Cardiology ◽

10.1016/j.jacc.2015.06.941 ◽

2015 ◽

Vol 66 (16) ◽

pp. C243

Author(s):

Zhanquan Jiao ◽

Guangping Li

Keyword(s):

Contrast Agent ◽

Signal Pathway ◽

Diabetic Rat ◽

Induced Apoptosis ◽

Rat Kidneys

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Curcin C inhibit osteosarcoma cell line U2OS proliferation by ROS induced apoptosis, autophagy and cell cycle arrest through activating JNK signal pathway

International Journal of Biological Macromolecules ◽

10.1016/j.ijbiomac.2021.11.156 ◽

2021 ◽

Author(s):

Fei Wang ◽

Peng Wu ◽

Siying Qin ◽

Yushan Deng ◽

Pan Han ◽

...

Keyword(s):

Cell Cycle ◽

Cell Cycle Arrest ◽

Cell Line ◽

Signal Pathway ◽

Osteosarcoma Cell Line ◽

Osteosarcoma Cell ◽

Cycle Arrest ◽

Induced Apoptosis

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The fate of SPE B after internalization and its implication in SPEB-induced apoptosis

Journal of Biomedical Science ◽

10.1007/s11373-007-9154-6 ◽

2007 ◽

Vol 14 (3) ◽

pp. 419-427 ◽

Cited By ~ 4

Author(s):

Chia-Wen Chang ◽

Wan-Hua Tsai ◽

Woei-Jer Chuang ◽

Yee-Shin Lin ◽

Jiunn-Jong Wu ◽

...

Keyword(s):

Induced Apoptosis ◽

Spe B

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Streptococcal Pyrogenic Exotoxin B-Induced Apoptosis in A549 Cells Is Mediated by a Receptor- and Mitochondrion-Dependent Pathway

Infection and Immunity ◽

10.1128/iai.72.12.7055-7062.2004 ◽

2004 ◽

Vol 72 (12) ◽

pp. 7055-7062 ◽

Cited By ~ 11

Author(s):

Wan-Hua Tsai ◽

Chia-Wen Chang ◽

Woei-Jer Chuang ◽

Yee-Shin Lin ◽

Jiunn-Jong Wu ◽

...

Keyword(s):

Protease Activity ◽

Time Course ◽

A549 Cells ◽

Affinity Column ◽

Dependent Manner ◽

Apoptotic Pathway ◽

Streptococcal Pyrogenic Exotoxin B ◽

Induced Apoptosis ◽

Dependent Pathway ◽

Spe B

ABSTRACT It has been shown that streptococcal pyrogenic exotoxin B (SPE B) can induce cells to undergo apoptosis. The present study is to dissect the role of SPE B protease and SPE B protein in the apoptotic process of A549 cells and to elucidate the SPE B-induced apoptotic pathway. Recombinant SPE B (rSPE B) and C192S, a mutant of SPE B without protease activity, were expressed in Escherichia coli and purified by using an affinity column. The apoptosis of A549 cells was assayed by propidium iodide staining, followed by flow cytometry analysis. Our results showed that SPE B induced apoptosis in a dose-dependent manner, whereas C192S did not. When cells were pretreated with rSPE B (2 μg/ml) for as briefly as 5 min and then incubated with C192S of 28 kDa, an apoptosis that is proportional to the period of pretreatment was observed but not with C192S of 42 kDa. These results suggest that the extracellular protease activity of rSPE B is required for the initiation of apoptosis and that the size of SPE B is important for an effective induction of apoptosis. The time course analysis revealed that molecules activated in apoptosis were in the following order: caspase-8 (1.5 h), t-Bid (2.5 h), Bax (3 h), cytochrome c release (6 h), caspase-9 (7 h), and caspase-3 (8 h). The overexpression of Bcl-2 inhibited depolarization of mitochondrial membrane, cytochrome c release, and apoptosis. The results of the present study suggest that SPE B-induced apoptosis is mediated through a receptor-like mechanism and a mitochondrion-dependent pathway.

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Dexamethasone Inhibits Podocyte Apoptosis by Stabilizing the PI3K/Akt Signal Pathway

BioMed Research International ◽

10.1155/2013/326986 ◽

2013 ◽

Vol 2013 ◽

pp. 1-9 ◽

Cited By ~ 12

Author(s):

Yu-Shengyou ◽

Yu Li

Keyword(s):

Renal Function ◽

Subcellular Distribution ◽

Akt Signaling ◽

Signal Pathway ◽

Protein Distribution ◽

Pi3k Inhibitor Ly294002 ◽

Antiapoptotic Proteins ◽

Apoptotic Death ◽

Induced Apoptosis ◽

Significant Concentration

Corticosteroids like dexamethasone (DEX) are well-established treatments for the glomerular disease that sustain renal function, at least in part, by protecting podocytes from apoptotic death. In this study, we found that PAN causes abnormal expression of the PI3K-binding protein CD2AP, reducing PI3K/Akt signaling and promoting podocyte apoptosis. In contrast, DEX restores CD2AP-PI3K-Akt-GSK3βsignaling, which promotes the activity of antiapoptotic proteins and inhibits the activity of proapoptotic proteins. In addition, we also found that CD2AP was aberrantly colocalized with p85. Normal CD2AP mRNA expression and subcellular protein distribution were maintained in the PAN + DEX group, and DEX coapplication also reduced CD2AP-p85 colocalization. PAN evoked a concentration-dependent decrease in p-Akt and p-GSK3βexpressions, with p-Akt expression reaching a nadir at 15 min and p-GSK3βexpression at 30 min. DEX treatment induced a concentration-dependent reversal of PAN-induced p-Akt and p-GSK3βdownregulation. The PI3K inhibitor LY294002 blocked p-Akt and p-GSK3βexpressions in podocytes. Cells treated with PAN exhibited a significantly higher apoptosis rate than untreated or vehicle-treated cells. Furthermore, LY294002 exacerbated PAN-induced apoptosis. DEX cotreatment caused a significant concentration-dependent decrease in PAN-induced apoptosis. These results strongly suggest that DEX protects podocytes by stabilizing the expression and subcellular distribution of CD2AP and by maintaining the expression of phosphor-activated Akt and GSK3β.

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Group A Streptococcus Induces Apoptosis in Human Epithelial Cells

Infection and Immunity ◽

10.1128/iai.67.9.4334-4339.1999 ◽

1999 ◽

Vol 67 (9) ◽

pp. 4334-4339 ◽

Cited By ~ 64

Author(s):

Pei-Jane Tsai ◽

Yee-Shin Lin ◽

Chih-Feng Kuo ◽

Huan-Yao Lei ◽

Jiunn-Jong Wu

Keyword(s):

Cell Death ◽

Epithelial Cells ◽

Group A Streptococcus ◽

Wild Type ◽

Group A ◽

Streptococcal Pyrogenic Exotoxin B ◽

Induced Apoptosis ◽

Isogenic Mutants ◽

Type Strains ◽

Spe B

ABSTRACT Internalization of group A streptococcus (GAS) by epithelial cells may have a role in causing invasive diseases. The purpose of this study was to examine the fate of GAS-infected epithelial cells. GAS has the ability to invade A-549 and HEp-2 cells. Both A-549 and HEp-2 cells were killed by infection with GAS. Epithelial cell death mediated by GAS was at least in part through apoptosis, as shown by changes in cellular morphology, DNA fragmentation laddering, and propidium iodide staining for hypodiploid cells. A total of 20% of A-549 cells and 11 to 13% of HEp-2 cells underwent apoptosis after 20 h of GAS infection, whereas only 1 to 2% of these cells exhibited spontaneous apoptosis. We further examined whether streptococcal pyrogenic exotoxin B (SPE B), a cysteine protease produced by GAS, was involved in the apoptosis of epithelial cells. The speB isogenic mutants had less ability to induce cell death than wild-type strains. When A-549 cells were cocultured with the mutant and SPE B for 2 h, the percentage of apoptotic cells did not increase although the number of intracellular bacteria increased to the level of wild-type strains. In addition, apoptosis was blocked by cytochalasin D treatment, which interfered with cytoskeleton function. The caspase inhibitors Z-VAD.FMK, Ac-YVAD.CMK, and Ac-DEVD.FMK inhibited GAS-induced apoptosis. These results demonstrate for the first time that GAS induces apoptosis of epithelial cells and internalization is required for apoptosis. The caspase pathway is involved in GAS-induced apoptosis, and the expression of SPE B in the cells enhances apoptosis.

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